A study of the angiotensin II and vasopressin pathways in brain is proposed. The cells of origin of these peptides will be determined by light microscopic immunocytochemistry. Vasopressin-containing pathways within the magnocellular neurosecretory system of the hypothalamus have been shown to project to the zona externa of the median eminence. We will examine the distribution of angiotensin II-containing neurons and their projected fibers to determine their relationship to vasopressin pathways. Rats with hereditary diabetes insipidus, treated and untreated, and Long-Evans control rats will be examined. Regional assay of angiotensin I and II and vasopressin in rat brain homogenates will be performed by radiommunoassay to correlate the immunocytochemical distribution of these peptides with their quantification. Renin substrate levels will be determined regionally. Radioimmunoassay of these peptides in blood from the pituitary portal plexus will be performed to determine possible pathways of synthesis and release. Peripheral plasma levels of these peptides will be measured for comparison. Re-examination of the angiotensin II and vasopressin pathways and the concentration of these peptides in various regions of brain and in the periphery will be made following the induction of DOCA-salt hypertension. The interaction of angiotensin II and vasopressin will be observed in control rats and in vasopressin deficient (DI) rats who have an apparent resistance to the development of this form of hypertension.